Preparation of spin-labeled opiates: morphine and codeine

The preparation of 6-spin-labeled codeine and morphine is described. Treatment of either 6-chlorocodide or 8-bromocodide with 4-amino-2,2,6,6-tetramethylpiperidino-1-oxyl free radical in dimethylformamide afforded 6-spin-labeled codeine. Similar treatment of 6-chloromorphide afforded 6-spin-labeled morphine. Exclusive formation of the 6-isomer in these reactions is explained by halide-ion-catalyzed isomerization of the 6-halo opiate to the 8-halo isomer followed by a normal SN2' displacement of the halogen. Both spin-labeled compounds displayed weak in vivo analgesic activity and did not bind appreciably to receptors in brain homogenate.